The purpose of this study is to identify genes causing non- insulin- dependent diabetes mellitus (NIDDM)-associated nephropathy (NIDDM-NEPH) in high risk African American families. At most, 30 percent of diabetic patients are susceptible to nephropathy with it's invariable progression to end-stage renal disease (ESRD) and high mortality rate. African American and Native American populations are known to be at higher risk for developing NIDDM and it's associated Nephropathy, relative to whites. However, in all populations, select diabetic families demonstrate multi-generational clustering of renal disease. An inherited basis for NIDDM-NEPH is also supported by reports that racial differences in the prevalence and severity of diabetes mellitus and hypertension, socioeconomic status and access to health care fail to fully account for the excess risk of NIDDM-NEPH observed in African Americans, relative to whites. In order to identify genes causing NIDDM- NEPH we will continue to identify, clinically characterize, and collect DNA from NIDDM affected sibling pairs concordant and discordant for NIDDM-NEPH. This phase of the project employs the unique "Family History of ESRD" database, independently compiled by the federally-funded ESRD Network 6 (Southeastern Kidney Council). This registry currently contains family history data from 7,600 incident patients with ESRD and contains data from more than 13,000 patients as of September, 1996 (60 percent of patients are African American; more than 35 percent have NIDDM-associated Nephropathy). Candidate genes will be screened for linkage to NIDDM-NEPH and a systematic genome wide survey for novel loci causing NIDDM-NEPH will be carried out. This effort will be formally linked to, and interact with, a parallel search for chromosome locations with evidence of linkage to insulin dependent diabetes associated nephropathy (IDDM-NEPH) in Caucasians through an interactive IRPG. The goal of this initial phase of the study is to locate chromosome regions with evidence of linkage to NIDDM-NEPH. The identification of NIDDM- NEPH genes would form a genetic basis for detection of high risk individuals and lead to development of intervention and treatment strategies for prevention of diabetic nephropathy, the most common etiology of ESRD in the U.S.